Singapore acts to stem bacterial resistance to antibiotics

10 July 2018

AMR IRG in RIE News, an NRF eZine

A feature story on AMR IRG in RIE News

The growing resistance of human infections to antimicrobial drugs has emerged as one of the most pressing public health problems in Singapore and the world. It is with this urgency that the National Research Foundation (NRF) announced the launch of the new Antimicrobial Resistance Interdisciplinary Research Group (AMR IRG) in January of this year. Administered by the Singapore MIT Alliance for Research and Technology (SMART), the AMR IRG will work in coordination with the new Singapore National Strategic Plan on Antimicrobial Resistance to define the mechanisms used by bacteria, parasites and viruses to resist antimicrobial drugs and use this knowledge to develop new resistance-busting therapeutics and new tools to rapidly diagnose AMR.

The rising tide of AMR is affecting public health and the economy in Singapore, Southeast Asia and the entire world. In Singapore, up to 50% of infections acquired in hospitals are resistant to front-line antibiotic therapies. This is illustrated by high incidence of methicillin resistance in infections by Staphylococcus aureus (MRSA) in healthcare facilities in Singapore.

More sobering, however, are predictions about the impact of AMR globally in the coming decades. While AMR currently results in about 700,000 deaths per year worldwide, recent studies predict an increase to 10 million deaths per year by 2050, outpacing the mortality of cancer. The economic burden is similarly staggering. In the US alone, antibiotic resistant bacteria infect 2 million people every year at a health care cost of S$27 billion. On a global scale, AMR is predicted to cost up to S$130 trillion by 2050.

In spite of this AMR crisis, academic and industrial research and development efforts have focused on non-communicable diseases such as cancer. In the biotechnology and pharmaceutical industry in 2014, there were about 800 oncology drugs but only 50 antimicrobial agents introduced into the development pipeline. Funding for AMR research also falls short from both biotechnology and academic sources. The US National Institute of Health (NIH), for example, allocated only 1.2% of grants for AMR research in 2009-2014, whereas 18.6% was allocated for cancer research.

The NRF has stepped in to address this critical unmet need for funding research and development of new AMR drugs and diagnostics by launching the SMART AMR IRG. With a five-year grant, the AMR IRG is co-led by Professor Peter Dedon, the Underwood-Prescott Professor of Biological Engineering at MIT, and Professor Peter Preiser, Chair of the School of Biological Sciences at Nanyang Technological University (NTU). They lead a team of 14 world-class professors from NTU, Duke-NUS, Tan Tock Seng Hospital, Singapore General Hospital, and MIT. The AMR IRG builds on strong collaborations with Singaporean scientists and clinician-scientists to integrate innovative MIT technologies into the development of new antimicrobial agents and diagnostic and surveillance tools.

AMR IRG leaders are optimistic about the impact of this joint effort to combat AMR, which builds on a decade-long track record of high-impact infectious disease research for several current AMR IRG team members. Professor Dedon notes that “It is a privilege to work with such a talented team of Singaporean and MIT researchers in the AMR IRG. This group brings exciting new technologies to bear on solving the most challenging problems posed by antimicrobial drug resistance in Singapore and around the world.” The feeling is reflected by Professor Preiser: “I am very excited about the unique opportunity the AMR research group offers to Singaporean and MIT researchers to work together to have a lasting impact on solving the global problem of antimicrobial drug resistance.”

Researchers everywhere agree that the key to tackling the AMR problem is to take a multi-pronged, highly interdisciplinary approach in developing novel ways to identify, rapidly respond to, and treat drug-resistant infections. The AMR IRG is doing just that by taking advantage of the technological, scientific and clinical strengths of MIT and Singapore, with expertise in emerging pathogens at Duke-NUS, in microbiomes and biofilms at NTU, in drug resistance and drug development at NTU and the A*STAR Experimental Therapeutics Centre, and in clinical studies at Singapore General and Tan Tock Seng Hospitals.

Research projects in the AMR IRG are approaching the threat of drug-resistant microbes from several directions. One thrust focuses on understanding the mechanisms used by bacteria, viruses and parasites to evade killing by drugs. This is illustrated by the poorly understood behavior of some bacteria to “hunker down” and become reversibly drug-resistant when faced with stresses caused by the human immune response to the infection or when growing as “biofilms” on solid surfaces such as urinary catheters. Defining these mechanisms is critical to developing resistance-reversing drugs. In another research thrust, AMR IRG researchers are developing rapid, sensitive and specific detection and diagnostic techniques for evaluating the spread of the resistant infections. For example, they are developing fast, cheap diagnostic tools made to be as simple as a pregnancy test and deployable in resource-limited environments. In yet another major set of projects, AMR IRG researchers are developing new therapeutics that combat resistant infections by exploiting the human immune system and microbiome to kill AMR microbes. They are also new small molecule and biological drugs and drug delivery technologies to combat resistant microbes.

The collaborative efforts of the AMR IRG will also have an impact on other aspects of life in Singapore. A major emphasis in the IRG is placed on translating discoveries into clinical studies and into new companies in Singapore. These companies will not only provide critical products to combat AMR but will also employ Singaporeans. Profs. Dedon and Preiser place a high value on the workforce training impact of the AMR IRG, with researchers jumping from the IRG to companies, agencies and universities in Singapore. The combination of innovative research and entrepreneurial spirit will have a significant impact on Singapore’s growing biotechnology industry. Ultimately, the goal of the AMR IRG is to use research to enhance the health and well-being of people in Singapore and the world.